Use Of Phenobarbitone Research Articles

Short Term Neurodevelopmental Outcome of Asphyxiated Term Neonates with Maintenance Phenobarbitone Therapy; Preliminary Findings of Ongoing Study in A Tertiary Care Hospital of Bangladesh

Phenobarbitone (PB) is the most commonly prescribed anticonvulsant worldwide to control neonatal seizure in asphyxiated neonates. In spite of limited clinical evidence regarding the best use of drug, their dose and duration: it appears that long term maintenance use of phenobarbitone might slow psychomotor development. Aim of this study was to assess the neuro developmental morbidity in asphyxiated neonates with long term anticonvulsant. This randomized clinical trial enrolled 79 asphyxiated neonates with HIE-II/ III, gestational age ≥ 35 completed weeks from January 2020-January 2021 where cases were categorized into three groups by lottery method. Group A and B received PHB 4mg/kg/day twice daily for 6 weeks and PHB 2mg/kg/day once daily for 2 weeks respectively while Group C didn’t receive any anti-seizure medication. Neurodevelopmental assessment was done at 6 months of age in every case. Data were analyzed by Chi-square & logistic regression test to find out the outcome. Among 79 cases mean gestational age was 37.74±0.98 weeks, M: F was 3:2 and most of them were inborn (51.4%). At 6 months 49 cases were analyzed, 19 were in group A and 15 cases from group B and 15 cases from group C. Cognitive impairment was found 5.844 times more in group A (52.63%) followed by group B (6.67%) and group C (13.33%) (p= 0.001). Group A had 5.844 times more cognitive impairment than other two groups (P= 0.039). No significant functional impairment in motor, speech, hearing and vision were found among the study groups. This study concluded that prolonged use of maintenance Phenobarbitone may impair cognitive function. The Journal of Ad-din Women's Medical College; Vol. 11 (2), July 2023; p 20-25

Predictors of Duration of Phenobarbitone Therapy in Seizures of Neonates with Hypoxic-Ischemic Encephalopathy

Objective: Perinatal asphyxia with hypoxic-ischemic encephalopathy associated with seizures is one of the leading cause of neonatal mortality and morbidity in Bangladesh. Phenobarbitone remains the drug of choice in treatment of neonatal seizures. This study was conducted to determine the predictors of duration of Phenobarbitone therapy in seizures of neonates with Hypoxic-Ischemic Encephalopathy (HIE). Methodology: The study was conducted in Neonatal Intensive Care Unit (NICU) of East West Medical College Hospital from 1st february 2016 to 31st january 2017 on fifty neonates with HIE and seizures. The dose and duration of phenobarbitone therapy for initial control of seizure was noted. Total duration of phenobarbitone therapy after control of seizure to prevent further recurrences was also noted. Follow up was given up to 3 months of age to see any recurrence of seizures. Results: Out of the 50 neonates,25 cases (50%) responded well within 24 hours. Mean duration of phenobarbitone therapy after initial control of seizure was 4.70 ± 2.93days and Mean total duration of therapy was 6.89 ± 3.58 days in cases who responded well within 24 hours.. 3 (6%) cases had recurrence of seizures. The recurrence cases required more than 72 hours for initial control of seizure (p 0.006) and had poor primitive reflexes and activity after initial control of seizure (p 0.0002). Mean duration of phenobarbitone therapy after initial control of seizures was 6.33 ± 6.11 days and Mean total duration of phenobarbitone therapy was also longer 9.67 ± 7.37 days. Conclusion: Neonates who have good initial response and have better reflexes required short duration of phenobarbitone therapy. It should be discontinued soon after control of seizure. Neonates with HIE III, those requiring more than 72 hours for initial response and poor reflexes after initial control of seizure may require longer duration of phenobarbitone therapy (more than 7 days) to prevent recurrence of seizures. Thus, judicious use of phenobarbitone will minimize the unnecessary non-specific treatment.

Review of Drug Utilization Studies in Neonatal Units: A Global Perspective.

Rational prescribing is challenging in neonatology. Drug utilization studies help identify and define the problem. We performed a review of the literature on drug use in neonatal units and describe global variations. We searched databases (EMBASE, CINAHL and Medline) from inception to July 2020, screened studies and extracted relevant data (two reviewers). The search revealed 573 studies of which 84 were included. India (n = 14) and the USA (n = 13) reported the most. Data collection was prospective (n = 56) and retrospective (n = 26), mostly (n = 52) from one center only. Sixty studies described general drug use in 34 to 450,386 infants (median (IQR) 190 (91–767)) over a median (IQR) of 6 (3–18) months. Of the participants, 20–87% were preterm. The mean number of drugs per infant (range 11.1 to 1.7, pooled mean (SD) 4 (2.4)) was high with some reporting very high burden (≥30 drugs per infant in 8 studies). This was not associated with the proportion of preterm infants included. Antibiotics were the most frequently used drug. Drug use patterns were generally uniform with some variation in antibiotic use and more use of phenobarbitone in Asia. This study provides a global perspective on drug utilization in neonates and highlights the need for better quality information to assess rational prescribing.

Efficacy of levetiracetam as the first line anti- epileptic drug in management of neonatal seizures

Background: Neonatal seizure management has not changed much in the last 50 years. Neuronal apoptosis in animal models and cognitive impairment in human subjects has been reported with the use of Phenobarbitone. Levetiracetam is advantageous as it is effective, well tolerated and has least drug interactions.Methods: This double blinded, randomized, parallel group, active controlled study was conducted among 66 neonates in the Neonatal intensive care unit of a tertiary care hospital for a period of 18 months. Neonates with seizures fulfilling the inclusion criteria were treated either with Phenobarbitone or Levetiracetam. Seizure control was defined as no seizure activity within 40 minutes of the administration of the first drug. Failure of first line agent was treated with Phenytoin. Neonates were observed for a period of 14 weeks for recurrence of seizure and any serious adverse effects.Results: Effective seizure control was achieved in 64.7% neonates in Levetiracetam group as compared to 31.2% in Phenobarbitone group (p <0.05). Early resumption of breast feeds within 6 hours of therapy was achieved in 73.5% neonates treated with Levetiracetam compared to 31.2% neonates treated with Phenobarbitone (p value = 0.001).Conclusions: Levetiracetam is a promising alternative as first line Anti-epileptic drug in neonates with seizures. Prolonged sedation was the adverse effect noted to Phenobarbitone that made breast feeding and neuro- assessment difficult. No serious adverse effects were seen with Levetiracetam.

Fast activity during EEG seizures in neonates

Paroxysmal fast activity (FA) has been proposed as a marker for epileptic networks. We explore the presence and significance of ictal FA on scalp video EEG seizures (EEG Sz) recorded in neonates. Forty two babies had 159 EEG Szs. The seizures were analysed for ictal FA, using a low frequency filter of 30 Hz. We explored the relationship of ictal FA to the occurrence of electroclinical and electrographic seizures, the use of phenobarbitone and to neurodevelopmental outcomes. Ictal FA occurred in 62 (39%) of the 159 EEG Szs. In the 62 seizures with ictal FA, 34 (55%) were electroclinical seizures (ECSz) and 28 (45%) were electrographic (ESz). In the remaining 97 seizures without ictal FA, 27 (28%) were ECSz and 70 (72%) ESz. There was a significant correlation (p=0.0006) between ictal FA and electroclinical seizures. There was no relationship between phenobarbitone and presence of ictal FA. There was no significant difference in the background EEG, neuroimaging abnormalities, neurodevelopmental impairment or post neonatal seizures between those with and without ictal FA. Ictal FA is highly correlated to the occurrence of clinical features during an EEG seizure. The presence of ictal FA does not appear to influence neurodevelopmental outcomes.

Cross‐sensitivity in a child with anticonvulsant hypersensitivity syndrome

We describe a fulminant picture of anticonvulsant hypersensitivity syndrome (AHS) and the possible role of nitrazepam. A 5-month-old boy developed fever and rash after the use of phenobarbitone. Allergy to phenobarbitone was suspected. Nitrazepam was substituted for seizure control. Over the next few days he progressively collapsed with fever, facial oedema and multi-organ involvement. The diagnosis of AHS was delayed because nitrazepam has not been implicated in the development of cross-sensitivity. AHS is a severe multi-organ reaction to aromatic anti-epileptic drugs. It has been thought to occur as a consequence of pre-existing pharmacogenetic and immunologic abnormalities. Careful selection of anti-epileptic drugs is essential as cross-sensitivity is common. Intermittent benzodiazepines have been recommended in managing breakthrough seizures in AHS. However, the structure of benzodiazepines contains aromatic rings and potential cross-reactivity cannot be totally ignored. Although we do not have direct proof, we believe that nitrazepam prolonged the clinical course.

Use of phenobarbitone for treating childhood epilepsy in resource-poor countries.

CITATION: Wilmshurst, J. M. & Van Toorn, R. 2005. Use of phenobarbitone for treating childhood epilepsy in resource-poor countries. South African Medical Journal, 95(6):392-395.

Expression of leptin and leptin receptor during the development of liver fibrosis and cirrhosis.

Leptin is involved in the regulation of food intake and is mainly secreted by adipocytes. Major secretagogues are cytokines such as TNF-alpha or IL-1. Leptin in turn upregulates inflammatory immune responses. Elevated leptin serum levels have been detected in patients with liver cirrhosis, a disease frequently associated with elevated levels of circulating cytokines as well as hypermetabolism and altered body weight. Recently, leptin has been detected in activated hepatic stellate cells in vitro and an involvement of leptin in liver fibrogenisis has been suggested. The current study was designed to further clarify the role of leptin in liver disease by characterizing leptin and leptin receptor expression in the development and onset of experimental liver fibrosis. Liver fibrosis and cirrhosis was induced in rats by use of phenobarbitone and increasing doses of CCl (4). Leptin and leptin receptor mRNA expression was determined by semiquantitative RT-PCR, protein expression by Western blot analysis and localization of leptin and its receptor by immunohistochemistry. Normal liver tissue does not express leptin, but leptin receptor mRNA. Increasing levels of leptin mRNA were detected in fibrotic and cirrhotic livers correlated to the degree of fibrosis. Leptin receptor mRNA expression was not significantly altered in damaged livers. Increasing levels of leptin were detected in fibrotic and cirrhotic livers, whereas protein expression of the receptor remained unchanged. Throughout different stages of liver fibrosis, leptin immunoreactivity was localized in activated hepatic stellate cells only, whereas immunoreactivity for the receptor was mainly seen on hepatocytes. In conclusion, leptin is expressed at increasing levels in activated hepatic stellate cells in vivo, which may therefore be a source of increased leptin tissue and serum levels contributing to the pathophysiology and morphological changes of chronic liver disease.

The epidemiology of epilepsy and learning disability.

The epidemiology of epilepsy and learning disability.

The Use of Phenobarbitone in the Management of Agitation and Seizures at the End of Life

This study investigated the role of phenobarbitone at the end of life by retrospective analysis of case notes. During a 3-year period, of the 748 patients who died in a 32-bed palliative care unit, 60 received phenobarbitone during the last week of life. Fifty-nine patients had advanced cancer, 16 of whom had cerebral involvement. Phenobarbitone was used to control agitation and seizures. It was administered via subcutaneous infusion at a dose of 600–2400 mg/day. The mean time from starting phenobarbitone to death was 34.1 hours. Phenobarbitone was well tolerated and effective, controlling physical and psychological agitation. No further seizures occurred. This study suggests that phenobarbitone has a useful role in the management of distressing symptoms in the last few days of life. J Pain S ymptom M anage 1999;17:363–368.

A study into the possible link between anti-epileptic drugs and the risk of fractures in Muckamore Abbey Hospital

The aims of the study were to investigate whether the effects of anti-epileptic drugs are related to the incidence of fractures; to investigate the role of certain other known factors that may contribute to prevention of fractures; and to advise about methods that may help to prevent the risks of fractures. A list was drawn up of all the patients who had had a fracture in the period 1990 – 1993 inclusive. Their BMI, mobility, diet, sunshine exposure, type of epilepsy (if epileptic), cause of fracture and drug regimen, were recorded. A control group of patients was matched for age, build and epilepsy diagnosis. The liquidised diet used in the hospital was very low in vitamin D and this was rectified by adding margarine instead of butter. The use of phenobarbitone, phenytoin and carbamazepine appeared significant (p=. 03) and also mobility factor (p =. 05). As a result of the survey, an audit is being carried out for diet, times and quantity of sun exposure, types and amount of exercise and monitoring of drug, therapy of vulnerable residents.

Prescribing practice in a mental handicap hospital: 1—ANTICONVULSANTS FROM 1978–87

This is the first of two articles which consider the use of medication in a mental handicap hospital over a ten‐year period. The present article reviews the use of medication to control epilepsy. The second will look at the use of psychotropic medication, that is, medication intended to alter mood, conciousness, or awareness.Prescription sheets and case notes of people resident in the hospital on 31st March 1978 and 31st March 1987 were studied to see trends in anticonvulsant usage during that period. There was a decline in the use of phenobarbitone and primidone, and an increase in the use of carbamazepine. The number of people on more than one drug did not alter greatly, but fewer were on more than two drugs by 1987. These results, and the continuing problem of people being prescribed more than one anticonvulsant at a time, are discussed.

Is terminal restlessness sometimes drug induced?

The case history of a terminally ill patient who developed continuous myoclonic jerking while comatose is presented. The potential for high dose opioids to produce central nervous system excitation, including twitching, myoclonic jerking and seizures, is highlighted. Attention is drawn to the possible contributory effects of phenothiazines and antihistamines by virtue of their ability to lower seizure threshold. The use of phenobarbitone to control such phenomena is suggested, and a brief review of other anticonvulsants which may be considered in palliative care is included.

Anticonvulsant medication in a mental handicap hospital: 1972-1982.

The prescription sheets for all patients in a mental handicap hospital on one day in 1972 and on the same date in 1982 were examined to identify trends in anticonvulsant medication over a 10-year period. There was a reduction in size of the hospital population associated with fewer very young and milder handicapped persons. Prescription of anticonvulsants fell slightly during the decade under study with a dramatic fall in the use of phenobarbitone, and a parallel increase in the prescription of carbamazepine. Other changes included the use of sodium valproate in a significant minority of patients and the occasional use of clonazepam in 1982, while phenytoin remained a first-rank anticonvulsant throughout the period under review. The proportions of patients on polytherapy did not change over the 10-year period, though the contribution of phenobarbitone to the combined drug regimes was significantly reduced.

Recessive lethals induced by styrene and styrene oxide in Drosophila melanogaster

Various advantages of Drosophila melanogaster in the detection of chemical mutagens have been extensively discussed [7,8]. The capability of Drosophila for metabolic activation of known precarcinogens into active electrophilic forms has been convincingly demonstrated by Vogel [11]. The existence of a mixed-function-oxidase system even in the gonadal tissues of Drosophila [1] enables sensitive detection of short-lived reactive intermediates. Furthermore, it enables the use of various enzyme inducers as well as inhibitors, as in mammalian experiments. Recently the use of sodium phenobarbiturate to induce the cytochrome P-450 system in Drosophila has been described by Magnusson and Ramel [3].In the present paper we report rather similar results of the exposure of Drosophila to phenobarbitone as a pretreatment to the exposure to styrene and styrene oxide. The use of phenobarbitone results in a further increase in the recessive-lethal frequency after exposure to styrene as well as after styrene oxide. Furthermore, the use of a potent epoxide hydrase inhibitor, trichloro-propane oxide [4], results in a significant rise in recessive lethals during exposure to styrene oxide.

PHENOBARBITONE IN RHESUS HÆMOLYTIC DISEASE: A Controlled Trial

A controlled trial of the use of phenobarbitone in the management of infants with rhesus hæmolytic disease is reported. Phenobarbitone was given in a dose of approximately 2 mg. per kg. body-weight 8-hourly as soon as the result of the Coombs' test on the cord-blood was known, and was continued until serum-bilirubin levels fell consistently. 30 control infants required 40 exchange transfusions; 30 treated infants required 21 exchange transfusions. This difference is significant at the 2% level. Considering only those infants who were considered to require immediate exchange transfusion at birth by the criteria used in the trial, then 15 control infants required 28 exchange transfusions and 13 treated infants required 19 exchange transfusions. This difference in the number of exchange transfusions per child does not reach clinical significance. If, however, the immediate exchange transfusions at birth are excluded from consideration, the difference between the groups becomes highly significant. 2 babies in the control group died as a direct result of hæmolytic disease or of exchange transfusion. In the treated group there was no neonatal mortality and no morbidity attributable to phenobarbitone. It is concluded that phenobarbitone given to infants affected by rhesus hæmolytic disease from the first few hours of life is of considerable value in reducing the need for exchange transfusion, especially in those mildly affected by rhesus incompatibility.